Pharmacological Modulation of Liver and Spleen Stiffness in a Cirrhotic Rat Model.

PURPOSE

Liver stiffness (LS) assesses liver fibrosis, while spleen stiffness (SS) is a promising marker for portal hypertension (PH), reflecting blood flow and vascular resistance. However, the response of LS and SS to vasoactive drugs is unclear. This study evaluates the effects of various PH-lowering drugs on LS and SS in a rat cirrhosis model.

PATIENTS AND METHODS

In this study, cirrhosis was induced in 43 male Wistar rats (8 weeks old) via intraperitoneal thioacetamide (TAA) injections (200 mg/kg, twice weekly for six weeks). Rats were divided into six groups: control (sodium chloride), metoprolol, udenafil, enalapril, terlipressin, and carvedilol. LS and SS were measured using μFibroscan. Mean arterial pressure (MAP), heart rate (HR), and portal vein pressure (PVP) were continuously monitored. Drugs were administered systemically, with data collected at 0, 15, and 30 minutes.

RESULTS

TAA-treated rats exhibited significantly higher LS and SS compared to controls (22.1 vs 4.2 kPa and 53.7 vs 27.7 kPa; P < 0.001). Changes in LS and SS correlated with PVP (r = 0.670 for LS and r = 0.867 for SS; P < 0.01). Metoprolol, udenafil, enalapril, and carvedilol significantly reduced PVP (22-34%, P < 0.05), accompanied by decreases in LS and SS (13-37%, P < 0.05). Terlipressin did not reduce LS or SS, likely due to opposing effects of increased MAP and reduced PVP.

CONCLUSION

In conclusion, combined LS and SS measurements may provide valuable non-invasive insights into patient responses and adherence to PH-lowering therapies.